Fig. 7 | Nature Communications

Fig. 7

From: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries

Fig. 7

Association of LPA variant classes with atherosclerosis. Mendelian randomization was performed using three genetic instruments: a weighted genetic risk score using variants conditioned on KIV2-CN at a 4 Mb window around LPA (GRS), a KIV2-CN score, and a combined GRS + KIV2-CN score, and compared to the observational effects. The genetic instruments were all normalized such that 1 unit increase in the score is equal to 1 SD increase in Lp(a). a Associations (HR and 95% CI) of incident coronary heart disease (1056 cases; 21,207 controls) and myocardial infarction (580 cases; 21,377 controls) with the Lp(a) measurement and with genetic instruments among the genotyped and imputed FIN individuals (exact values in Supplementary Table 30). b Associations (Beta and 95% CI) of Lp(a) measurements and respective genetic instruments with standardized markers of subclinical atherosclerosis (CAC and AAC) among whole genome sequences of African Americans from 1701 JHS and 932 MESA participants, as well as European Americans from 1536 FHS and 1651 MESA participants (Supplementary Table 12). These data indicate that (1) a comprehensive Lp(a) genetic instrument (GRS + KIV2-CN) provides improved risk assessment compared to the Lp(a) phenotype, and (2) further stratifying this comprehensive instrument into separate Lp(a) variant classes provides additional risk stratification in that genomic sequence variants independent of KIV2-CN (i.e., GRS) have a stronger influence on clinical atherosclerosis compared to KIV2-CN. AAC Abdominal aortic calcium, CAC coronary artery calcium, CI confidence interval, FHS Framingham Heart Study, FIN FINRISK, GRS genetic risk score, HR hazard ratio, JHS Jackson Heart Study, KIV2-CN kringle IV-2 copy number, Lp(a) lipoprotein(a), Lp(a)-C lipoprotein(a) cholesterol, MESA Multi-Ethnic Study of Atherosclerosis